Lecture 7 Flashcards
What is the adrenal gland?
There are 2 adrenal glands located about the upper pole of each kidney
It is composed of a capsule, inner medulla, and outer cortex
Cortisol and aldosterone are made from cholesterol
Cortisol is a glucocorticoid because it increases plasma glucose levels
Aldosterone is a mineralcorticoid because it promotes salt and water retention by the kidney
Slides 1-4
What are the 3 levels of the cortex in the adrenal gland?
Zona glomerulosa- secretes mineralcorticoids, mainly aldosterone
Zona fasciculata- secretes glucocorticoids, mainly cortisol
Zona reticularis- secretes androgens
Slide 2
What is the medulla in the adrenal gland?
Adrenal medulla chromaffin cells secrete epinephrine and norepinephrine (NE)
Slide 2
What are the steroid hormones of the adrenal cortex?
Cortisol
Aldosterone
Dehydroepiandrosterone
All derivatives of cholesterol
Slide 5
What is cortisol?
Produced by zona faciculata of adrenal cortex from cholesterol containing low density lipoprotein
Primary glucocorticoid steroid in humans
Most of it is transported by corticosteroid-binding globulin (CBG)
Binds to intracellular receptors within target cells and translocates to the nucleus to modulate gene transcription
All nucleated tissues in body have receptors for glucocorticoids (GR)
Slides 6-7
How to glucocorticoids (GR) translocate into nucleus?
GR primarily located in the cytoplasm
In its unbound form it is complexed to a chaperone protein such as the heat shock protein hsp90
Binding of cortisol causes the chaperone to dissociate from the GR and this allows the cortisol GR complex time translocate to the nucleus, where the complex associates with glucocorticoid response elements (GREs) to either enhance or diminish gene expression
Slide 7
What are the 8 functions of cortisol?
- Increase plasma glucose concentration
- Anti-inflammatory activity
- Optimize the vascular responsiveness to catecholamines
- Enhance glomerular filtration by increasing vasodilation of the afferent arterioles
- Decrease the ability of osteoblasts to synthesize new bone
- Decrease absorption of Ca from the GI tract
- Acts on CNS to induce alterations in mood and cognition
- May cause insulin resistance and many features of the metabolic syndrome, a co morbid condition of glucose intolerance, hypertension
How does cortisol increase plasma glucose concentration?
3 ways
- By enhancing mobilization of amino acids from proteins and enhance ability of liver to convert these amino acids into glucose and glycogen by activating gluconeogenesis
- Increase protein catabolism and decrease new protein synthesis in muscles
- Increase lipolysis and allow additional glycerol to the liver for gluconeogenesis
Slide 8
How does cortisol have anti inflammatory activity?
It enhances the synthesis of lipoprotein that inhibits phospholipase A2 (enzyme responsible for producing arachnoid acid, inflammatory precursor for prostaglandins and leukotrienes)
Inhibits release of pro inflammatory cytokine, interleukin 2 and reduces proliferation of t lymphocytes
Inhibits release of histamine from mast cells
Immunosuppressive activity can be used against rejection of transplanted organs
Inhibits bradykinin & serotonin inflam effects
Impairs cell mediated immunity
Decreases circulating eosinophils, basophil, lymphocyte counts
Slides 9-12
How does cortisol optimize the vascular responsiveness to catecholamines?
Cortisol is necessary for the maintenance of normal blood pressure in the level of arterioles
Hypocortisolism May lead to hypotension
What may excess cortisol cause?
Cushing syndrome
Truncal adiposity, hypertension, loss of subcutaneous adipose tissue in the extremities with easy bruising, loss of bone mineral, muscle weakness, hyperglycemia
Slide 15
What may insufficient cortisol cause?
Insufficient cortisol may cause addison’s syndrome
Chronic adrenal insufficiency
Hypocortisolism
What is aldosterone?
Mineralcorticoid produced by zona glomerulosa of the adrenal cortex from cholesterol-containing low-density lipoprotein
Primary regulator of salt balance and water retention
Bound to albumin
Mainly control the homeostasis of Na, water retention and arterial pressure
Also affect homeostasis of K+
Can influence acid base balance by promoting H secretion and HCO3 reabsorption
Slides 17-18
What are the factors affecting aldosterone secretion?
The renin-angiotensin system, potassium, and ACTH all stim the glomerulosa cells of adrenal cortex to secrete aldosterone
Blockage of aldosterone generation with angiotensin converting enzyme (ACE) inhibiting drugs reduces angiotensin II production and markedly decreases plasma aldosterone
Slide 19
Study the actions of aldosterone slide 20
Ok
What is the role of aldosterone in disease?
In hypertension, ACE inhibitors are effective in reducing blood pressure, implying their renin-angiotensin- aldosterone axis was overactive
Aldosterone secretion increases congestive heart failure (increased salt retention would aggregate the situation)
Increase aldosterone synthesis can occur in patients with tumors of the glomerulosa cell
Hypertension and hypokalemia frequently develop in patients with hyperaldosteronism
Aldosterone increases fibrosis with certain tissues (myocardium, blood vessel wall)
Slide 21
What are adrenal androgens?
Andrenal androgens are produced by the zona reticularis of the adrenal cortex from cholesterol-containing low density lipoprotein
Dehydroepiandrosterone (DHEA)
Androstenedione
Andrenal androgens have weak androgenic activity than testosterone
Slides 22-23
What are adrenal androgens in males vs females?
In males, andrenal androgens are converted to testosterone in the testes
Less physiological significance because greater amounts of testosterone are produced in the testes
In females, adrenal androgens are major source of androgenic compounds and are converted by the granulosa cells of the ovarian follicle into 17β-estradiol, adrenal androgens are important source of this after menopause following the cessation of ovarian estrogens
Slides 24-25
What do the adrenomedullary chromaffin cells synthesize?
Adrenomedullary chromaffin cells synthesize epinephrine and norepinephrine from the amino acid tyrosine
Hormones secreted by the adrenal medulla
Slide 26
What are the 5 types of adrenergic receptor types and responses?
α1- excitatory, prefer NE, increase smooth muscle contract
α2- inhibitory, prefer NE, decrease motility
β1- excitatory, likes NE and E the same, increased rate and strength of contraction
β2- inhibitory, only takes E, bronchiolar dilation, arteriolar vasodilation in heart and skeletal muscle
β3- excitatory, low affinity for NE/E, enhance lipolysis in adipose tissue and thermogenesis in skeletal muscle
Slide 27
What is the hypothalamic-pituitary-adrenocortical axis?
Corticotropin releasing hormone (CRH) from the hypothalamus stims corticotrophs of the anterior pituitary to secrete adrenocorticotropic hormone (ACTH) which stims the adrenal cortex to synthesize and secrete cortisol
Paraventricular nucleus (PVN) also make another hormone, arginine vasopressin (AVP), which is a potent ACTH secretagogue
Slide 30-31
What is the preprohormone pro-opiomelanocortina (POMC)?
39 amino acid peptide hormone secreted by the corticotrophs of the anterior pituitary, ACTH, can also be produced by ectopic sources
Pituitary corticotrophs synthesize ACTH by complex post translational processing of a large precursor protein called pro-opiomelanocortin (POMC)
POMC is a precursor for ACTH and variety of peptide hormones like β-LPH, γ-MSH, J peptide, α-MSH, CLIP, etc
Slide 32-33
Study the pituitary hormone and it’s targets slide 34
The hypothalamus controls the pituitary glands, pituitary hormones produced and the responses of the different target tissues
The release of the anterior pituitary hormones is stimulated by releasing hormones and suppressed by inhibiting hormones
A hormone that stims release of another hormone with growth effect is know as a trophic hormone
